Almost 35 years after Institut Pasteur scientists discovered the HIV-1 virus (a discovery that was recognized by the 2008 Nobel Prize in Medicine), AIDS remains an unacceptable scourge. AIDS is now one of the leading causes of death in the world for teenagers and women of childbearing age. The number of new infections is currently increasing in Eastern Europe and there are about 6,000 new cases in France each year1.

It is estimated that some 37 million people are currently infected, all around the world

6,000 new cases in France each year

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Cause

HIV stands for human immunodeficiency virus. It is contracted by sexual contact, contaminated blood, and mother-to-child transmission. In the latter case, transmission of the virus from mother to child can take place:

during the last trimester of pregnancy, by HIV passage through the placental barrier during blood exchange between the mother and the fetus;

during childbirth.

while breastfeeding.

Taking antiretroviral therapy during pregnancy can bring the rate of transmission to less than 1%.It targets T lymphocytes, cells that are vital for a healthy immune system. Without treatment, HIV gradually weakens the immune system, and sufferers develop serious diseases over the long term, known as “opportunistic diseases” as they are caused by microorganisms that are harmless for those with a healthy immune system.

Acquired immunodeficiency syndrome (AIDS) is the final stage of HIV infection, when those infected develop one or more opportunistic diseases.

Symptoms

The clinical symptoms of HIV vary according to the different stages of the disease. The first stage is known as primary infection, when those infected may have no symptoms or may develop flu-like symptoms after an incubation period of one to several weeks (high fever, muscle pain, headaches, diarrhea).

After the primary infection stage comes an asymptomatic stage that can last for several years. During this period, the virus is still present and those infected remain contagious. HIV gradually weakens the immune system, leading to other symptoms such as weight loss, fever, skin infections, diarrhea, and cough.

If left untreated, the disease develops into Acquired Immunodeficiency Syndrome, or AIDS, the final stage of HIV infection. This stage is characterized by the emergence of “opportunistic” diseases, which take advantage of the weakened immune system. AIDS sufferers may contract any number of bacterial, fungal, and parasitic infections, as well as some cancers.

Treatment

There is currently no treatment that can completely eliminate HIV from the body.Treatments have been developed to stop HIV spreading in seropositive patients, allowing them to maintain a functional immune system. These treatments are known as triple therapies or multiple therapies, since they combine several antiretroviral molecules. Antiretroviral drugs can cause side effects, including nausea, vomiting, tiredness, loss of appetite, fever, diarrhea, and skin reactions.

It is recommended to initiate treatment as soon as possible after infection. This helps to keep the immune system as intact as possible, to reduce the chronic inflammation induced by the infection and also to reduce the risk of HIV transmission. Unfortunately, most HIV infections are only detected after many years of infection, and only 60% of people infected with HIV worldwide have access to treatment.

Resistance to the virus in rare cases

. A tiny percentage of Caucasians (less than 1%) are even resistant to HIV infection. This spontaneous control is often associated with particular HLA genes backed up by very strong CD8 + T cell responses. There are also some individuals who control the virus after receiving a treatment. Other very rare people are even resistant to the infection (so-called remission patients).This resistance is caused by a mutation in the “CCR5” chemokine receptor gene, which is a receptor for the virus. Cases of “paradoxical couples” (that is to say, "serodiscordant" couples where one observes, without being able to explain it, that the seronegative partner is not infected by the HIV-positive partner), prostitutes or children born to mothers infected and resistant to the infection are under study.

Epidemiology

Emergence in the 1980s

AIDS was first described in 1981, but retrospective studies on serum specimens from Zaire (now Congo) indicate that the virus has existed since 1959. Other studies have shown that HIV has been circulating in humans for longer than that, probably since the end of the 19th century.

It is possible that HIV was originally contained within an isolated population before spreading as a result of increasing urbanization and population movements at the beginning of the 20th century. HIVs have an animal reservoir. At least forty African monkey species (including chimpanzees, gorillas, green monkeys, mangabeys, and mandrills) are naturally infected by retroviruses closely related to HIV known as simian immunodeficiency viruses (SIVs). The infection does notnot result in AIDS in some of these species.

One of the two human viruses, HIV-2, is closely related to the SIV that infects mangabey monkeys living in West Africa. It is therefore possible that humans may have been contaminated after being bitten by these monkeys. HIV-1 may have been spread by chimpanzees and gorillas; some of whom living in Cameroon and Gabon are carriers of an SIV that is closely related to HIV-1.

Rapid spread

Since 1981, when the HIV epidemic was discovered, the virus has spread from Africa to North America and subsequently to Europe. Homosexuals with multiple partners were the first to be affected in the United States. The epidemic was then observed in blood transfusion patients, hemophiliacs, and drug addicts, emphasizing the risks of blood-borne transmission. In Asia, the disease only emerged around 1986-87, firstly in Thailand and then in other Southeast Asian countries. Prostitution and intravenous drug use were major factors in the spread of HIV in these countries. The most common mode of HIV transmission worldwide is currently heterosexual intercourse. It is estimated that some 37 million people are currently infected (see AIDS in figures).

At the Institut Pasteur

The work of the research teams covers most of the current priority research areas: the mechanisms by which HIV replicates in human cells the mechanisms responsible for immunodeficiency, and for chronic inflammation the immune responses controling the virus, , the mechanisms of the virus persistence despite effective treatment, metabolic changes associated with HIV infection, the role of the microbiome the effects of the treatments on the virus and immune responses, the factors of remission and candidate vaccines.

This research is carried out in close partnership with the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), and the Vaccine Research Institute (VRI).

VIDEO (in French) - HIV: towards new treatments

Almost 35 years after the discovery of HIV-1, AIDS remains an unacceptable scourge, particularly affecting the poorest countries and populations: 37 million people are living with HIV / AIDS in the world and, in France, another 6000 new infections per year. Antiretrovirals now provide good control of the disease but not a cure. Françoise Barré-Sinoussi, Nobel Prize for Medicine for the discovery of HIV, explains the current challenges of research on this virus, including new ways that could lead to a cure. (in French).